Generalizability of the Results of Efficacy Trials in First-Episode Schizophrenia: Comparing Outcome and Study Discontinuation of Groups of Participants in the Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) Trial

Lyliana G Nasib*, Inge Winter-van Rossum, Nicolaas P A Zuithoff, Zimbo S R M Boudewijns, Stefan Leucht, René S Kahn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: In the majority of randomized controlled trials (RCTs) conducted in schizophrenia populations, patients suffering from a substance use disorder (SUD) or suicidality are excluded. Excluding these patients from RCTs might impact the generalizability of results. The aim of this study is to determine whether excluding patients with suicidality and/or SUD impacts RCT results on symptomatic remission, premature study discontinuation, symptom severity, and social functioning. Methods: Across Europe and Israel, 481 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder, based on DSM-IV criteria, were recruited between May 26, 2011, and May 15, 2016, for the Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) trial. Baseline characteristics and follow-up assessments were compared between patients with versus without baseline SUD and/or suicidality. Results: A total of 446 patients met eligibility criteria for the OPTiMiSE trial and initiated amisulpride treatment, of whom 404 (91%) had data available on suicidality, SUD, duration of illness, and CDS score. Of the 360 eligible patients with baseline data on suicidality and SUD, 106 patients had comorbid suicidality and/or SUD while 254 patients had neither of these comorbidities. No significant differences in the likelihood to achieve symptomatic remission or to prematurely discontinue the study were found when comparing comorbid versus non-comorbid patients (P= .27). There were no significant differences in symptom severity and social functioning between the groups. Comorbid patients had a higher level of depressive symptoms and more impaired social functioning compared to non-comorbid patients. Discussion: Excluding first-episode schizophrenia patients with comorbidities from clinical trials unlikely affects key outcome measures. It is recommended to include patients with comorbidities in clinical trials while carefully monitoring suicidality and implementing safety plans to gain insight into efficacy and safety of treatment in this substantial patient population.

Original languageEnglish
Article number46380
Number of pages10
JournalThe Journal of clinical psychiatry
Volume84
Issue number3
DOIs
Publication statusPublished - 29 Mar 2023

Keywords

  • Amisulpride/therapeutic use
  • Antipsychotic Agents/adverse effects
  • Europe/epidemiology
  • Humans
  • Psychotic Disorders/diagnosis
  • Schizophrenia/drug therapy
  • Substance-Related Disorders/epidemiology
  • Treatment Outcome

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